During the present report period, efforts have been focused on two fronts; the development and application of methods for scale-up production of the new anti-HIV agent, michellamine B; and, the bioassay-guided isolation of new potential antitumor leads from marine organisms and plants. Because of its novel structure, unusual anti-viral activity against both HIV-1 and HIV-2 and favorable physicochemical attributes, michellamine B, discovered by LDDRD from the leaves of Ancistrocladus sp. novum, has been selected by NCI as a candidate for stage B (INDA-directed) preclinical development. Preparative isolation and purification methods were developed for multi-gram quantities of the compound needed for preliminary pharmacokinetics and toxicity studies. These efforts facilitated the isolation of other new alkaloids present in the source plant in minor amounts. Purification and complete structure elucidation of these other components are continuing. Chemical and anti-viral activity studies of other related species of Ancistrocladus confirm that michellamine B is present primarily in the leaves, and that plants containing the compound have a limited geographical distribution. Efforts are continuing on further refinement of separation/purification methods to allow a production rate of 2g/week of pure michellamine B to support stage B preclinical development. Also during this report period, increasing efforts have been directed to the study of extracts found active in the NCI primary anticancer screen. Isolation and purification of active components from an anticancer extract of the sponge Cribrochalina spiculosa are currently being pursued.